Perspectives on mitochondrial relevance in cardiac ischemia/reperfusion injury

Abstract

Cardiovascular disease is the most common cause of death worldwide and in particular, ischemic heart disease holds the most considerable position. Even if it has been deeply studied, myocardial ischemia-reperfusion injury (IRI) is still a side-effect of the clinical treatment for several heart diseases: ischemia process itself leads to temporary damage to heart tissue and obviously the recovery of blood flow is promptly required even if it worsens the ischemic injury. There is no doubt that mitochondria play a key role in pathogenesis of IRI: dysfunctions of these important organelles alter cell homeostasis and survival. It has been demonstrated that during IRI the system of mitochondrial quality control undergoes alterations with the disruption of the complex balance between the processes of mitochondrial fusion, fission, biogenesis and mitophagy. The fundamental role of mitochondria is carried out thanks to the finely regulated connection to other organelles such as plasma membrane, endoplasmic reticulum and nucleus, therefore impairments of these inter-organelle communications exacerbate IRI. This review pointed to enhance the importance of the mitochondrial network in the pathogenesis of IRI with the aim to focus on potential mitochondria-targeting therapies as new approach to control heart tissue damage after ischemia and reperfusion process.

1,3,8-Triazaspiro[4.5]decane Derivatives Inhibit Permeability Transition Pores through a FO-ATP Synthase c Subunit Glu119-Independent Mechanism That Prevents Oligomycin A-Related Side Effects

“…The most studied phenomenon in which PTP opening triggers extensive cell death and tissue function loss is ischemia reperfusion injury (IRI) [ 9 , 10 , 11 , 12 ]. In ischemic environments, the PTP is blocked due to the high proton concentration or by cellular acidification due to glycolytic pathways being activated in the absence of oxygen [ 13 ].…”

“…In ischemic environments, the PTP is blocked due to the high proton concentration or by cellular acidification due to glycolytic pathways being activated in the absence of oxygen [ 13 ]. Otherwise, during reperfusion, PTP opening is prompted by generation of reactive oxygen species (ROS), pH recovery and mitochondrial Ca 2+ accumulation [ 12 , 13 ].…”

Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia–reperfusion injury: unfolding new epigenetic frontiers

“…Abnormality of mitophagy induces LDL accumulation and mitochondrial dysfunction, thereby aggravating diabetic cardiomyopathy [ 49 ]. In the context of ischemia, mitophagy plays important roles in cardiac ischemia and protects against cardiac injury by mitochondrial clearance [ 50 ]. Mitophagy also is involved in the cardioprotection against acute ischemic injury by inhibition of Nrf2 and endoplasmic reticulum stress [ 51 ].…”

Mitochondria-derived Vesicles mediate Mito-nuclear Trafficking of Cargo

“…Ischemia is caused by hypoxia and nutrient deficiency, followed by reperfusion through reoxygenation process. The reperfusion process produces free radicals, which damages the mitochondria [51]. We observed a reduction in nuclear PDH during ischemia and reperfusion compared to control conditions (Figure 5G).…”